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Immune cells drive glaucomatous vision loss

Immune cells developed from early exposure to bacteria contribute to vision loss in glaucoma sufferers, according to a new study into causes of the disease.

The research team from Massachusetts Eye and Ear and the Massachusetts Institute of Technology (MIT) suggests high intraocular pressure triggers an autoimmune response that attacks the neurons in the eye, similar to immune responses in bacterial infections, leading to vision loss.

“Our work shows that there is hope for finding a cure for glaucoma, or even preventing its development entirely, if we can find a way to target this pathway,” the study’s co-senior author Dr Dong Feng Chen, a vision scientist at Mass. Eye and Ear and associate professor of ophthalmology at Harvard Medical School, said.

“Current glaucoma therapies are designed solely to lower eye pressure; however, we’ve known that even when patients with glaucoma are treated and their eye pressure returns to normal, they can still go on to have vision loss. Now, we know that stress from high eye pressure can initiate an immune response that triggers T cells to attack neurons in the eye.”

"Our work shows that there is hope for finding a cure for glaucoma."

Dong Feng Chen, Vision scientist at Mass. Eye and Ear

Increased eye pressure is the most important risk factor for glaucoma, however, little is known as to how and why patients with high pressure develop permanent blindness.

Additionally, some glaucoma patients do not have elevated eye pressure, and some patients still experience optic nerve degeneration and vision loss even after their eye pressure is under control with treatment.

However, the new mechanism helps to explain the series of events leading to permanent blindness from glaucoma.

When the pressure in the eye increases, it induces the expression of heat shock proteins – a family of proteins that develop in response to stressful conditions. This leads to a response from immune cells called memory T cells that are programmed to respond to heat shock proteins.

The memory T cells attack the neurons of the retina, leading to degeneration of the optic nerve and often-permanent loss of vision. T cell responses are essential in the development of progressive vision loss following elevated eye pressure.

Tests of the immune response to heat shock proteins were found both in mice and in human patients with glaucoma. The team first detected T cells in the retina of a mouse model of glaucoma, which motivated experiments to determine if the T cells played a role in neuron loss.

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The team studied three groups of mice with glaucoma – some without T cells, some without B cells, and some without T or B cells. Overwhelmingly, they saw a loss of neurons in the mice only if the mice contained functional T cells.

More strikingly, development of glaucoma-inducing T cells required early exposure to bacteria; mice never exposed to bacteria were free from glaucoma under elevated eye pressure.

Aside from mouse models, researchers also studied blood samples from patients with primary open angle glaucoma (POAG). In humans, they observed T cells responses similar to the mice that were more than five-fold higher in patients with POAG compared to samples from patients without POAG.